Circulating Tumour Cells and PD-L1-positive Small Extracellular Vesicles: the Liquid Biopsy Combination for Prognostic Information in Patients with Metastatic Non-small Cell Lung Cancer

Overview

Journal Br J Cancer

Specialty Oncology

Date 2023 Nov 17

PMID 37973956

Authors

Zahra Eslami-S

Luis Enrique Cortes-Hernandez

Lea Sinoquet

Ludovic Gauthier

Valentin Vautrot

Laure Cayrefourcq

Laure Avoscan

William Jacot

Stephane Pouderoux

Marie Viala

Quentin Dominique Thomas

Pierre-Jean Lamy

Xavier Quantin

Jessica Gobbo

Catherine Alix-Panabieres

Affiliations

Soon will be listed here.

Abstract

Background: Circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), and extracellular vesicles (EVs) are minimally invasive liquid biopsy biomarkers. This study investigated whether they predict prognosis, alone or in combination, in heterogenous unbiased non-small cell lung cancer (NSCLC) patients.

Methods: Plasma samples of 54 advanced NSCLC patients from a prospective clinical trial. CtDNA mutations were identified using the UltraSEEK™ Lung Panel (MassARRAY® technology). PD-L1 expression was assessed in small EVs (sEVs) using an enzyme-linked immunosorbent assay.

Results: At least one ctDNA mutation was detected in 37% of patients. Mutations were not correlated with overall survival (OS) (HR = 1.1, 95% CI = 0.55; 1.83, P = 0.980) and progression-free survival (PFS) (HR = 1.00, 95% CI = 0.57-1.76, P = 0.991). High PD-L1 sEV concentration was correlated with OS (HR = 1.14, 95% CI = 1.03-1.26, P = 0.016), but not with PFS (HR = 1.08, 95% CI = 0.99-1.18, P = 0.095). The interaction analysis suggested that PD-L1 sEV correlation with PFS changed in function of CTC presence/absence (P interaction = 0.036). The combination analysis highlighted worse prognosis for patients with CTCs and high PD-L1 sEV concentration (HR = 7.65, 95% CI = 3.11-18.83, P < 0.001). The mutational statuses of ctDNA and tumour tissue were significantly correlated (P = 0.0001).

Conclusion: CTCs and high PD-L1 sEV concentration correlated with PFS and OS, but not ctDNA mutations. Their combined analysis may help to identify patients with worse OS.

Trial Registration: NCT02866149, Registered 01 June 2015, https://clinicaltrials.gov/ct2/show/study/NCT02866149 .

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